This invention relates to water soluble complexes or inclusion compounds of steroid compounds and use of same in pharmaceutical preparations.
Various steroid compounds are used in aqueous mediums, topical ointments and the like as pharmaceutical preparations for treating eye and skin disorders. Steroid compounds generally are substantially insoluble in water unless in the form of a salt. Consequently, when used in an aqueous medium, other additives are required to assist in maintaining the steroid compound in suspension. Aqueous suspensions containing steroid compounds which are not a salt or various esters usually must be shaken before use in order to obtain a uniform dispersion of the steroid compound and thereby insure that an accurate dosage is administered.
An example of such preparations are topical ophthalmic suspensions containing a corticosteroid, such as prednisolone acetate, dexamethasone and hydrocortisone acetate, and used for treatment of ocular inflammation. The patient must follow a dosage schedule and shake the bottle to fully suspend the corticosteroid so that the full dosage is delivered to the eye. Even though the label usually includes specific instructions to shake the bottle well before using, patients usually do not shake the bottle at all or shake it only a few times. In a study of commercially available corticosteroid suspensions reported in Amer. J. of Opthal., 87:210-214 (1979), it was observed that, without shaking up to 15 times, concentrations ranging from less than 29% up to less 61% of the maximum concentration of the drug would be delivered to the eye. Thus, an inadequate dosage would be administered under ordinary condition of use.
During long term storage, steroid compounds tend to settle to the bottom of the bottle and become caked. In some cases the steroid compound and/or solid additives in the preparation deposit in the bottle tip and plug it so that the preparation cannot be squeezed out without first unplugging the tip with a needle or the like.